Prime Merger Sub, LLC

Patent Trials and Appeals Board

Aug 24, 2021

2020005051 (P.T.A.B. Aug. 24, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/309,566 11/08/2016 Steven J. Thomas 15840.0022 4635
26359 7590 08/24/2021
Maynard Cooper & Gale, PC (Birmingham)
1901 Sixth Avenue North
2400 Regions/Harbert Plaza
Birmingham, AL 35203-2618
EXAMINER
VISONE, THOMAS J
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
08/24/2021 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
JThomas@maynardcooper.com
ipdocket@maynardcooper.com
tebbert@maynardcooper.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte STEVEN J. THOMAS and KATIE C. MOWRY1
____________

Appeal 2020-005051
Application 15/309,566
Technology Center 1600
____________

Before DONALD E. ADAMS, JOHN G. NEW, and
TIMOTHY G. MAJORS, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies Prime Merger Sub, LLC as the real
party-in-interest. App. Br. 3.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1–8, 10–13, and 23–31. Specifically,
claims 1–8, 10–13, 23–24, and 30–31 stand rejected as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination of over Skardal et
al. (WO 2014/040026 A2, March 13, 2014) (“Skardal”), M.G. Roubelakis et
al., Amniotic Fluid and Amniotic Membrane Stem Cells: Marker Discovery,
2012 STEM CELLS INT’L 1–9 (2012) (“Roubelakis”), Jansen et al. (US
2011/0212064 A1, September 1, 2011) (“Jansen”), and Koob et al. (US
2014/005227 A1, February 20, 2014) (“Koob”), and as evidenced by
H. Niknejad et al., Properties of the Amniotic Membrane for Potential Use
in Tissue Engineering, 15 EURO. CELLS AND MATERIALS 88–99 (2008)
(“Niknejad”) and Segall et al (US 2003/0022147 A1, January 30, 2003)
(“Segall”).
Claim 25 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Skardal, Roubelakis, Jansen, Koob,
and Squillace (US 2007/0260109 A1, November 8, 2007) (“Squillace”).
Claims 26 and 28 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Skardal, Roubelakis,
Jansen, Koob, and Shoseyov et al. (US 2011/0269667 A1, November 3,
2011) (“Shoseyov”).
Claim 27 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Skardal, Roubelakis, Jansen, Koob,
and D. Brett, A Review of Collagen and Collagen-based Wound Dressings,
20(12) WOUNDS 347–56 (2008) (“Brett”).
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Claim 29 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Skardal, Roubelakis, Jansen, Koob,
and S. Zhou et al., Demineralized bone promotes chondrocyte or osteoblast
differentiation of human marrow stromal cells cultured in collagen sponges,
6(1) CELL TISSUE BANK. 33–44 (2005) (“Zhou”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to a method of treating a
wound including applying a wound care treatment to the wound, the wound
care treatment including a preparation composed of morselized amnion
tissue and amniotic fluid cells adsorbed to a porous collagen matrix and
optionally, glycosaminoglycan. Spec. Abstr.

REPRESENTATIVE CLAIM
Independent claim 1 is representative of the claims on appeal and
recites:
1. A method of treating a wound comprising:

adding amnion tissue and amniotic fluid cells to a first
solution thereby forming a first suspension,

cryopreserving the first suspension,

thawing the first suspension,

providing a porous matrix including a mammalian
collagen and optionally, glycosaminoglycan (GAG),

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combining the thawed first suspension with the porous
matrix to form a preparation including a first portion of the
amnion tissue and a second portion of the amniotic fluid cells
adsorbed to the porous matrix, and

applying the preparation to a mammal,

wherein the amnion tissue of the first portion adsorbed to
the porous matrix is (i) morselized, (ii) has an average particle
size in a range of about 10 micrometers to about 1000
micrometers, and (iii) includes organized amniotic extracellular
matrix (ECM), amniotic tissue cells and growth factors contained
within the ECM and amniotic tissue cells.

App. Br. 28.

ISSUES AND ANALYSIS
We agree with, and adopt, the Examiner’s findings, reasoning, and
conclusion that the claims are obvious over the teachings and suggestions of
the combined cited prior art. We address Appellant’s arguments below.

A. Claims 1–8, 10–13, 23–24, and 30–31

Issue 1
Appellant argues that the Examiner erred by finding that the combined
cited prior art teaches or suggests morselized amnion tissue having an
average particle size in a range of about 10 μm to about 1000 μm, and
including organized amniotic extracellular matrix (“ECM”), amniotic tissue
cells and growth factors contained within the ECM and amniotic tissue cells.
App. Br. 15.

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Analysis
The Examiner finds that the claim 1 recites “morselized amnion
tissue,” which the Examiner interprets as encompassing amnion tissue
subjected to milling, mincing, grounding, micronizing, etc. Final Act. 2.
The Examiner interprets the claim term “about,” as recited throughout the
claims as meaning plus or minus 20% of the recited value(s). Id.
The Examiner finds that Skardal teaches a first composition
comprising amniotic tissue that is milled, minced, or ground into a fine
powder. Final Act. 2 (citing Skardal Abstr., 17). The Examiner finds that
Skardal teaches that the amniotic tissue is prepared to avoid disrupting the
structure of the tissue. Id. at 2–3 (citing Skardal 17; see also 16 (teaching
embodiments that avoid steps “that may disturb or destroy the complex
infrastructure of the biostructure”)). The Examiner also finds that Skardal
teaches embodiments in which the amniotic membrane is not decellularized.
Id. at 3 (citing Skardal 17). The Examiner reasons that the composition
taught by Skardal would thus retain organized amniotic extracellular matrix
(“ECM”) and amniotic tissue cells, with growth factors contained within the
ECM and amniotic tissue cells. Id.
The Examiner further finds that Skardal further teaches that the
composition is absorbed onto a porous matrix, such as a porous collagen
(e.g., Type I and/or Type II) hydrogel or sheet, to produce a second
preparation useful to promote wound healing, such as skin wounds, in
mammals. Final Act. 3 (citing Skardal Abstr., 3, 23, 24, 41, 44). The
Examiner finds that Skardal also teaches that the matrix can further comprise
glucosaminoglycans (“GAG”). Id. (citing Skardal 23).
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The Examiner finds that Skardal does not teach that the first
composition comprises amniotic fluid cells. Final Act. 4. However, the
Examiner finds that Roubelakis teaches amniotic fluid comprises amniotic
fluid stem cells (“AFSCs”). Id. (citing Roubelakis, 2 § I.I.I). The Examiner
concludes that a person of ordinary skill in the art would have been
motivated to add amniotic fluid cells to the composition taught by Skardal,
because Roubelakis teaches that these cells advantageously share a
multipotent mesenchymal phenotype, and exhibit higher proliferation
potential and a wider differentiation potential compared to adult
mesenchymal stem cells. Id. (citing Roubelakis, 2 § I.I.I). The Examiner
also points out that Roubelakis further teaches that “AFSCs or AMSCs
[amniotic membrane stem cells] can be used as tools in regenerative
medicine.” Id. (citing Roubelakis, 6).
The Examiner finds that Skardal and Roubelakis do not expressly
teach cryopreserving the first suspension or thawing the first suspension.
Final Act. 5. The Examiner finds that Jansen teaches cryopreserving
placental products in a cryoprotectant solution comprising 5% DMSO (a
cryoprotectant) in saline and subsequently storing the cryopreserved product
in a vial. Id. (citing Jansen ¶¶ 148, 220–244). The Examiner also finds that
Jansen teaches cryopreserving the placental products in a cryoprotectant
solution comprising protein, such as 1% to about 15% albumin by weight.
Id. (citing Jansen ¶ 148). The Examiner concludes that a person of ordinary
skill in the art would have been motivated to modify the combined teachings
of Skardal and Roubelakis with the cryoporeservation method taught by
Jansen to advantageously cryopreserve the first suspension for long-term
storage prior to use, including, e.g., thawing the first preparation and
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absorbing it onto a porous matrix to produce a second preparation useful to
promote wound healing in mammals. Id. Furthermore, concludes the
Examiner, it would have been a matter of routine experimentation using
standard laboratory techniques available at the time of filing to determine the
optimal DMSO and protein concentrations in saline to cryopreserve
advantageously the first suspension taught by Skardal and Roubelakis. Id.
(citing In re Aller, 220 F.2d 454, 456 (C.C.P.A. 1955) (holding that “where
the general conditions of a claim are disclosed in the prior art, it is not
inventive to discover the optimum or workable ranges by routine
experimentation”)).
The Examiner finds that applying the suspension taught by Skardal
and Roubelakis (after cryopreserving and thawing, as taught by Jansen) to
the porous matrix taught by Skardal would form a preparation including a
first portion of the amnion tissue and a second portion of the amniotic fluid
cells adsorbed to the porous matrix. Final Act. 5. The Examiner
acknowledges that the combination of Skardal, Roubelakis, and Jansen does
not expressly teach that the amniotic membrane tissue of the first portion
adsorbed to the porous matrix has an average particle size in a range of
about 10 to about 1000 micrometers. Id. at 6. The Examiner finds that
Koob, which teaches a similar wound healing method, teaches the use of
micronized amniotic membrane tissue having a preferred particle size of,
e.g., 150 to 350 μm. Id. (citing Koob ¶ 78). The Examiner concludes that a
person of ordinary skill in the art would have been motivated to combine the
teachings of Koob with those of Skardal, Roubelakis, and Jansen, because
Koob further teaches average particle size can advantageously be used to
control the release of collagen types IV, V, and VII, cell-adhesion bio-active
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factors, including fibronectin and laminins, and other components, from the
micronized amnion tissue. Id. (citing Koob ¶ 80).
Appellant argues that the compositions taught by Skardal are prepared
by one of two methods, with each method including a number of variants.
App. Br. 13. According to Appellant, the first method includes isolating an
amniotic membrane from a mammal, washing the amniotic membrane,
lyophilizing the amniotic membrane, and grinding the amniotic membrane to
form a powder. Id. at 13–14. Appellant contends that the second method
includes the steps of the first method, plus forming a mixture of amniotic
membrane powder, pepsin, and a solution, centrifuging the mixture to form a
supernatant and a pellet, and removing the supernatant, thereby forming
solubilized amniotic membrane (“SAM”). Id. at 14. Appellant argues that
Skardal teaches that the amniotic membrane powder or SAM is then
incorporated within or applied to the surface of a scaffold. Id. Appellant
acknowledges that Skardal teaches that the scaffold may include a hydrogel,
electrospun scaffold, foam, mesh, sheet, patch, or sponge. Id.
Appellant acknowledges that Skardal teaches that in certain instances
the methods may or may not include decellularization of the amniotic
membrane. App. Br. 14. Appellant also acknowledges that Skardal further
teaches that the methods may include cutting the membrane into pieces and
milling or mincing the membrane. Id. Appellant argues that the Examiner
has interpreted these teachings of Skardal to mean that the amniotic
membrane-based scaffold compositions for inducing wound healing and
tissue regeneration taught by Skardal include morselized amnion tissue that
retains organized amniotic ECM and amniotic tissue cells with growth
factors contained therein. Id.
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Appellant disagrees for three reasons. First, Appellant argues, the
membrane-based scaffold taught by Skardal includes either amniotic
membrane powder, as produced via the first method described above, or
SAM, as produced via the second method. App. Br. 14. Appellant contends
that none of the amniotic membrane-based scaffolds taught by Skardal
includes minced, milled or cut pieces of amniotic membrane. Id. Instead,
argues Appellant, the amniotic membrane-based scaffolds taught by Skardal
include a lyophilized amniotic membrane that has been ground into a
powder, and optionally, solubilized. Id. Appellant asserts that amniotic
membrane-based scaffolds produced in this manner do not include
morselized amnion tissue, morselized amnion tissue having an average
particle size in a range of about 10 to about 1000 micrometers, and includes
organized amniotic extracellular matrix (ECM), amniotic tissue cells and
growth factors contained within the ECM. Id. at 14–15. Appellant contends
that amniotic tissue cells lyophilized membrane ground into a powder
inherently disrupts the ECM so that it is no longer organized. Id. at 15.
Appellant next argues that, with respect to Skardal’s teachings related
to decellularization, cutting, mincing and milling of the amniotic membrane,
the Examiner has interpreted these teachings to mean that the amniotic
membrane preparations of Skardal include either cut, minced or milled
pieces of amnion tissue instead of a lyophilized powder or SAM. Final Act.
15. Appellant contends that the Examiner has misinterpreted these
teachings. Id. According to Appellant, the steps of decellularizing,
refraining from decellularizing, cutting, mincing and milling the amniotic
membrane referred to by Skardal are simply additional steps that may be
optionally applied to the two methods described above. Id. By way of
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example, Appellant notes that Skardal teaches cutting amnion membrane
into pieces prior to lyophilizing the membrane before converting the cut
pieces into powder or SAM. Id. (citing Skardal, 47–48). Therefore,
Appellant contends, although it is true that the amniotic membrane is cut
into pieces, those pieces do not remain in the composition that is combined
with a porous scaffold or used to treat a patient. Id. Instead, argues
Appellant, the pieces are lyophilized and ground. Id. Appellant also points
to claim 15 of Skardal, which recites forming an amniotic membrane powder
by lyophilizing membrane, and to claim 18, which depends from claim 15,
and recites the additional step of decellularizing the amniotic membrane. Id.
Appellant therefore asserts that Skardal’s teachings related to
decellularization, cutting, mincing and milling of the amniotic membrane
mean that these steps are incorporated into one of the two steps discussed
above. App. Br. 15. Appellant does not deny that Skardal teaches cutting,
mincing and milling of the amniotic membrane and refraining from
decellularizing the amniotic membrane, but argues that these steps occur in
combination with lyophilizing the amniotic membrane to form a powder or
SAM. Id. at 15–16. Appellant therefore asserts that the preparations taught
by Skardal do not include morselized amnion tissue adsorbed to a porous
matrix, with an average particle size in a range of about 10 to about 1000
micrometers, and including organized amniotic extracellular matrix (ECM),
amniotic tissue cells and growth factors contained within the ECM and
amniotic tissue cells, as claimed.
Third, Appellant argues, Skardal teaches the shortcomings of using
allografts and cellularized graft products for wound treatment, as taught by
the art at the time of invention. App. Br. 16 (citing Skardal, 1–2). Appellant
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contends that Skardal thus identifies shortcomings of allograft and
cellularized graft products for wound treatment, including immune rejection,
expensive production and complicated regulatory and financial hurdles. Id.
Appellant next points to Skardal’s succeeding teaching that “there is a
need in the art for a wound healing and tissue engineering product that has
high clinical efficiency, and that does not require a cellular component, but
instead retains the bioactivity of a cellular treatment. The present invention
satisfies this unmet need.” App. Br. 17 (quoting Skardal, 2). Therefore,
Appellant asserts, Skardal expressly teaches that its compositions for
inducing wound healing and tissue regeneration taught do not require a
cellular component. Id. Nevertheless, Appellant contends, the Examiner
concludes that the composition taught by Skardal includes morselized
amnion tissue that retains organized amniotic ECM and amniotic tissue cells
with growth factors contained therein. Id.
Finally, Appellant contends that the remaining references do not cure
the alleged deficiencies of Skardal. App. Br. 18. Appellant asserts that the
Examiner relies upon Roubelakis as teaching adding amniotic fluid cells to
the method taught by Skardal. Id. According to Appellant, Jansen is relied
upon by the Examiner as teaching adding the first preparation to a first
solution thereby forming a first suspension, cryopreserving the first
suspension and thawing the first suspension. Id. Appellant argues that
Koob is relied upon by the Examiner as teaching use of micronized amnion
tissue having a preferred particle size of, e.g., 150 to 350 μm. Id. Appellant
asserts that none of these references teaches the contested limitation of claim
1. Id.
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We are not persuaded by Appellant’s arguments. With respect to
Appellant’s first argument, that none of the amniotic membrane-based
scaffolds taught by Skardal includes minced, milled or cut pieces of
amniotic membrane (see App. Br. 14), Skardal expressly teaches:
In one embodiment of the method of the present invention, the
amniotic membrane is cut into pieces. The membrane may be cut
using a pair of scissors, a knife, a pair of forceps, a scalpel, a
microtome, and the like. In another embodiment, the amniotic
membrane is milled, minced, or grounded into a fine powder.
Formation of the amniotic membrane derived powder may be
carried out by any method known in the art. For example, in one
embodiment, membrane pieces are placed within a cryogenic
impact grinder. An exemplary cryogenic impact grinder is the
Spex SamplePrep 6870 Freezer/Mill®, which allows for cycling
of cooling phases and milling phases during the grinding of
samples.

Skardal, 17 (emphasis added). The plain language of the Skardal thus
contemplates at least two alternative embodiments: (1) in which the
membrane is cut into pieces using of scissors, knife, forceps, scalpel, a
microtome, or the like; and (2) the amniotic membrane is milled, minced, or
grounded into a fine powder.
Skardal also teaches that “[i]n one aspect, the composition is a
hydrogel scaffold that comprises amniotic membrane.” Skardal, Abstr.
Specifically Skardal teaches that:
[i]n one embodiment, the present invention provides an amniotic
membrane-based tissue engineering scaffold, and methods of
making the same. In one embodiment, the scaffold is a hydrogel,
wherein amniotic membrane or SAM is incorporated within the
hydrogel. In another embodiment amniotic membrane or SAM is
applied [i.e., adsorbed onto] to a scaffold.

Id. at 8 (emphasis added).
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In short, and contrary to Appellant’s argument, Skardal teaches a
number of different embodiments, but it expressly teaches cutting
(morselizing) the pieces of amniotic membrane, leaving the ECM intact, and
adsorbing onto the scaffold.
With respect to Appellant’s second argument, i.e., that Skardal cites
the prior art as discouraging the use of cellular components in its invention
(see Appeal Br. 16), Skardal teaches:
In another embodiment, the amniotic membrane is not
decellularized. In some aspects, it may be beneficial to not
decellularize the amniotic membrane. While not wishing to be
bound by any particular theory, it is believed that decellularizing
the amniotic membrane may remove various components of the
membrane which are important for wound healing applications.
Thus, while the present invention is not limited by whether the
amniotic membrane is or is not decellularized, the eventual use
for the produced composition may dictate whether or not to
include a decellularization step in the present method. Further, in
some instances, it is beneficial to only partially decellularize the
membrane.

Skardal, 17. Skardal thus expressly teaches that, in some circumstances, it
might be desirable to maintain the cells in the amniotic membrane.
Additionally, this passage of Skardal also emphasizes the desirability of
maintaining “various components of the membrane which are important for
wound healing applications,” e.g., the ECM. Id.
With respect to Appellant’s third argument, that the remaining
references cited by the Examiner do not cure the alleged deficiencies of
Skardal, we have explained why Appellant’s arguments with respect to
Skardal are not persuasive. Appellant’s third argument is consequently
moot.

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Issue 2
Appellant argues that the Examiner erred because a person of ordinary
skill in the art would have had no motivation to modify the teaching of
Skardal in view of the teachings of Roubelakis, Jansen, and Koob, as
evidenced by Niknejad and Segall. App. Br. 18.

Analysis
Appellant argues that Roubelakis teaches that that amniotic fluid stem
cells (“AFSC”) exhibit a multipotent mesenchymal phenotype and higher
proliferation potential and wider differentiation potential compared to adult
mesenchymal cells. App. Br. 19. Appellant contends that the Examiner
therefore argues that a person of ordinary skill in the art would have been
motivated to add AFCS to the first preparation taught by Skardal, because
the cells advantageously share multipotency. Id.
Appellant argues that, although Roubelakis teaches of certain
“promising” benefits of AFSC, there is no teaching by Roubelakis or
Skardal with respect to any benefit of combining AFSTs with amniotic
membrane or amniotic membrane stem cells (“AMSCs”). App. Br. 19.
Appellant argues further that Roubelakis teaches that such benefits may not
be realized because of variations in the phenotype, heterogeneity and
absence of a single marker expressed only in AFSC or AMSCs. Id.
Appellant notes that Roubelakis also teaches that because of these
unresolved problems with AFSC and AMSCs, their potential use in
therapeutic applications may be compromised. Id.
Consequently, Appellant reasons, when read as a whole, Roubelakis
does not teach combining AFSCs with AMSCs but, rather, Roubelakis
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teaches that, because there are different types of AFSCs and AMSCs (e.g.,
different phenotypes and heterogeneity), such cells should be isolated and
distinguished based upon their different gene expression patterns, which are
affected by culture conditions. Id. at 19–20.
Appellant reasons that, because a skilled artisan would have
recognized that combining AFSCs with AMSCs would exacerbate the
problems of different phenotypes and heterogeneity, the artisan would have
avoided combining AFSCs with AMSCs, and would therefore have had no
motivation to modify the teachings of Skardal with those of Roubelakis.
App. Br. 20.
The Examiner responds that Roubelakis cannot reasonably be
understood as teaching away from using AFSCs and AMSCs for
regenerative medicine; rather, it only suggests that homogenous populations
should be isolated to study the individual properties of AFSCs and AMSCs.
Ans. 19–20. The Examiner reasons that Appellant cannot escape that fact
that, as found in the Final Office Action, Roubelakis provides a clear
teaching, suggestion, and motivation specifically to utilize AFSCs in
regenerative medicine, which would reasonably lead one of ordinary skill in
the art to wound healing applications. Id. at 20.
We do not find Appellant’s argument persuasive. Roubelakis teaches
that “amniotic fluid cells (AF[S]Cs) represent a heterogeneous population
derived from the three germ layers,” and that “[t]he majority of the AFSCs,
isolated [by a previously described method] shared a multipotent
mesenchymal phenotype and exhibited higher proliferation potential and a
wider differentiation potential compared to adult MSCs.” Roubelakis, 2.
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With respect to AFMCs, Roubelakis teaches that “[a]mniotic
membrane stem cells (AMSCs) include two types, the amniotic epithelial
cells (AECs) and the amniotic membrane mesenchymal stem cells (AM-
MSCs) derived from the amniotic epithelial and the amniotic mesenchymal
layers, respectively,” and that “AM-MSCs, similarly to AF-MSCs, exhibited
a higher proliferation rate compared to MSCs derived from adult sources and
a multilineage differentiation potential into cells derived from the three germ
layers.” Roubelakis, 2. Roubelakis summarizes that “AFSCs or AMSCs
can be used as tools in regenerative medicine: establishment of culture
conditions with minimal or no animal substances.” Id. at 6.
Skardal expressly contemplates the addition of stem cells to its
compositions. Skardal teaches that “[i]n one embodiment, the scaffolds are
seeded with one or more populations of cells to form an artificial organ
construct,” and that “it may be desirable to include stem cells.” Skardal,
36–37.
We agree with the Examiner that a person of ordinary skill in the art,
upon comprehending the teachings of Skardal and Roubelakis, would have
been motivated to combine the teachings of the references to add amniotic
stem cells to the compositions of Skardal, as directly suggested by the latter
reference.
Appellant also repeats its argument that the preparation taught by
Skardal for use with a porous scaffold includes either a lyophilized amniotic
powder or SAM, exclusively. App. Br. 20. Appellant argues that there
would have been no motivation or reason to cryopreserve a lyophilized
amniotic power or SAM, as taught by Jansen, including storage in a
cryopreservation medium. Id. Appellant asserts that the purpose of
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cryopreserving amniotic membrane is to preserve the structure of the
membrane, and that such a purpose is not applicable to a lyophilized and
ground amniotic powder or SAM. Id.
We have explained supra why we are not persuaded that Skardal
teaches only adding a lyophilized amniotic powder or SAM to the
membrane, but also teaches the addition of morselized membrane itself, so
as to preserve the features of the membrane itself, including cells. We agree
with Appellant that lyophilizing a powder of the membrane, as taught by
Skardal, would obviate the need for cryopreservation. However, we are
persuaded by the Examiner’s findings and conclusion that it would have
been obvious to a person of ordinary skill in the art to preserve the combined
amniotic membrane and cells for use at a future time, as taught by Jansen
Finally, Appellant repeats its argument that Skardal teaches that
cellularized graft products for wound treatment have shortcomings such as
immune rejection, expensive production and complicated regulatory and
financial hurdles. App. Br. 21. We have explained supra why we are not
persuaded by this argument, viz., that Skardal expressly contemplates the use
of cellularized membrane with its scaffold, and of seeding the scaffold as
well with exogenous cells, including stem cells. For these reasons, we again
fail to be persuaded by Appellant’s arguments.

B. Claim 25
Claim 25 depends from claim 1 and recites: “The method of claim 1
including thawing the first suspension in a volume of saline.” App. Br. 32.
Appellant repeats the arguments presented supra, and contends that
Squillace, upon which the Examiner relies as teaching the limitation of claim
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25, fails to cure the alleged deficiencies of Skardal, Roubelakis, Jansen, and
Koob. Id. at 22.
We are not persuaded. We have explained why Appellant’s
arguments with respect to the Examiner’s rejection of claim 1 are not
persuasive. Squillace is directed to methods of sterilization and
decellularization of allografts or xenografts. Squillace, Abstr. Specifically,
Squillace teaches, with respect to thawing cryopreserved tissue, that:
Thawing and rinsing are performed aseptically. The rinsing
procedure must be performed immediately after the thawing
procedure. The allograft package is first thawed at room
temperature and then in warm saline (32° C. to 42° C.). The
saline step is supposed to rapidly thaw the tissue without
adversely affecting cellular viability.

Squillace ¶ 83. We agree with the Examiner that Squillace teaches the
limitation of claim 25, and we affirm the Examiner’s rejection.

C. Claims 26 and 28
Claims 26 and 28 depend from claim 1. Claim 28 is representative
and recites: “The method of claim 1 wherein the porous matrix is composed
of a flowable, granulated, cross-linked tendon collagen and GAG.” App. Br.
32. Appellant repeats the arguments presented supra, and contends that
Shoseyov, upon which the Examiner relies as teaching the limitation of
claims 26 and 28, fails to cure the alleged deficiencies of Skardal,
Roubelakis, Jansen, and Koob. Id. at 23.
We are not persuaded. We have explained why Appellant’s
arguments with respect to the Examiner’s rejection of claim 1 are not
persuasive. Shoseyov is directed to a method of promoting wound healing,
comprising administering a therapeutically effective amount of a
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procollagen. Shoseyov, Abstr. Specifically, Shoseyov teaches the use of
TENOGLIDE, a porous matrix of cross-linked bovine Type I collagen and
glycosaminoglycan (GAG). Shoseyov ¶ 260. Shoseyov also teaches the use
of INTEGRA Flowable Wound Matrix, an advanced wound care matrix
comprised of a granulated cross-linked bovine tendon collagen and
glycosaminoglycan, and further teaches that the granulated collagen-
glycosaminoglycan is hydrated with saline and applied in difficult to access
wound sites and tunneled wounds. Shoseyov ¶ 237. We agree with the
Examiner that Shoseyov teaches the limitation of claims 26 and 28, and we
affirm the Examiner’s rejection.

D. Claim 27
Claim 27 depends from claim 1 and recites: “The method of claim 1
wherein the porous matrix is composed of a sheet of native, non-denatured
collagen.” App. Br. 32. Appellant repeats the arguments presented supra,
and contends that Brett, upon which the Examiner relies as teaching the
limitation of claim 27, fails to cure the alleged deficiencies of Skardal,
Roubelakis, Jansen, and Koob. Id. at 24.
We are not persuaded. We have explained why Appellant’s
arguments with respect to the Examiner’s rejection of claim 1 are not
persuasive. Brett is a review article addressing collagen and collagen-based
wound dressings. Brett, Abstr. Specifically, Brett teaches the use of PURA
COL, which is a “100% pure bovine-derived collagen in its native [i.e., non-
denatured], triple-helix format,” which comes as absorbent collagen sheets.
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Brett, 356. We agree with the Examiner that Brett teaches the limitation of
claims 27, and we affirm the Examiner’s rejection.

E. Claim 29
Claim 29 depends from claim 1 and recites: “The method of claim 1
including forming the porous matrix by digesting mammalian collagen in
pepsin, pouring the digested mammalian collagen into a mold and freeze-
drying the digested mammalian collagen within the mold.” App. Br. 33.
Appellant repeats the arguments presented supra, and contends that Zhou,
upon which the Examiner relies as teaching the limitation of claim 29, fails
to cure the alleged deficiencies of Skardal, Roubelakis, Jansen, and Koob.
Id. at 25.
We are not persuaded. We have explained why Appellant’s
arguments with respect to the Examiner’s rejection of claim 1 are not
persuasive. Zhou teaches that demineralized bone promotes chondrocyte or
osteoblast differentiation of human marrow stromal cells cultured in
collagen sponges. Zhou, Title. Specifically, Zhou teaches producing a
porous, three-dimensional collagen matrix by: (1) digesting bovine
(mammalian) collagen in pepsin; (2) pouring the digested mammalian
collagen into a mold; and 3) freeze-drying the digested mammalian collagen
in the mold. Zhou 2. We agree with the Examiner that Zhou teaches the
limitation of claims 29, and we affirm the Examiner’s rejection.

CONCLUSION
The rejection of claims 1–8, 10–13, and 23–31 as unpatentable under
35 U.S.C. § 103(a) is affirmed.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED

Claim(s)
Rejected
35 U.S.C.
§ 
Reference(s)/Basis Affirmed Reversed
1–8, 10–
13, 23–24,
30–31
103(a) Skardal, Roubelakis,
Jansen, Koob
1–8, 10–13,
23–24, 30–
31

25 103(a) Skardal, Roubelakis,
Jansen, Koob,
Squillace
25
26, 28 103(a) Skardal, Roubelakis,
Jansen, Koob,
Shoseyov
26, 28
27 103(a) Skardal, Roubelakis,
Jansen, Koob, Brett
27
29 103(a) Skardal, Roubelakis,
Jansen, Koob, Zhou
29
Overall
Outcome
1–8, 10–13,
23–31